Clinical Safety and Efficacy Evaluation of NanoLithium® NP03 in Patients With Mild-to-severe Alzheimer's Disease

Alzheimer's Disease Clinical Trial

— NanoLi®_AD  

Official title:

Prospective, Multicenter, First Part Randomized, Placebo-controlled, Parallel-group, Double-blind Period Followed by Open-label Trial Period to Evaluate Clinical Safety & Efficacy of NanoLithium® NP03 in Patients With Mild-to-severe Alzheimer's Disease: Proof-of-concept Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05423522
• Other study ID #: 2021 NanoLi-CT01
• Status: Recruiting
• Phase: Phase 2
• Start date: May 20, 2022
• Est. completion date: April 2025

Study information

• Verified date: April 2024
• Source: Medesis Pharma SA
• Contact: Solène GUILLIOT
• Phone: +33 4 67 10 71 60
• Email: solene.guilliot[@]medesispharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This proof-of-concept study will assess safety, tolerance, and efficacy of NanoLithium® NP03 in patients with mild-to-severe Alzheimer's Disease (AD).

Description:

This French Study is a prospective, multicenter, randomized (1:1), placebo-controlled, parallel-group, double-blind period followed by an open-label trial period to Evaluate Clinical Safety and Efficacy of NanoLithium® NP03 in Patients With Mild-to-severe Alzheimer's Disease.

Patients will be randomized into two treatment arms:

• NanoLithium® NP03 (N=34)

• Placebo (N=34)

The first phase will consist of a double blind 12-week -period, which will be followed by an open-label 36-week period for each arm.

A total of 18 clinical or phone call visits are scheduled during this study. During the follow-up, clinical, biological, electrophysiological, imaging assessments and questionnaires will be performed to determine the safety, efficacy, and disease-modifying effect of NanoLithium® NP03.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: April 2025
• Est. primary completion date: January 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

Inclusion Criteria:

• Male and female patients between 50 and 90 years inclusive;

• Sufficient clinical and paraclinical information for the diagnosis of AD according to the international diagnosis criteria from McKhann G. M. et al. 2011;

• Patient presents clinically significant behavioral and psychological symptoms of dementia (BPSD) requiring medication in the opinion of the study physician (at least one item of the Neuropsychiatric Inventory-12 [NPI-12] with a score = 4);

• Mild to-severe AD with a Minimal Mental State Examination (MMSE) score from 10 to 26 included;

• Symptomatic treatments of AD (acetylcholinesterase inhibitors and memantine) and psychotics drugs (benzodiazepines, antidepressants, anxiolytics, neuroleptics) are allowed but need to be maintained during at least 4 weeks before inclusion and during the follow-up;

• Female patient of childbearing potential must be willing to use an efficient birth control method during the study and until 5 days after the end of the treatment.

A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus, tubal ligation).

The following are acceptable contraceptive methods: - Established use of oral, injected, or implanted hormonal methods of contraception - Intrauterine system or placement of an intrauterine device - Double barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, film, cream, or suppository

• True abstinence [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception]

• Male patient must be willing to use male contraception (condom) during the study;

• Patient must have availability of a person ("study partner" or caregiver) who has frequent and sufficient contact with the patient, can provide accurate information regarding the patient's behavior, cognitive, and functional abilities as well as his/her health throughout the study, and agrees to provide information at investigational site visits;

• Patient is willing and able to give informed consent. If the study patient is not competent, a legally authorized representative must provide informed consent on his/her behalf, and the patient must provide assent;

• Patient affiliated to French social security;

• Patient is willing to and can comply with the study protocol requirements, in the opinion of the investigator.

• If the patient took part to another therapeutic clinical trial, he/she must systematically observe a wash-out period of > 4 weeks, or of > 6 months if he/she received a biologic disease modifying treatment (antibodies targeting the ß-amyloid protein or the p-Tau protein) or 5 half-lives of investigational drug(s), whichever is longer.

Exclusion Criteria:

• Patient with genetic form of AD (known genetic mutation);

• Patient with major physical or neurosensory problems likely to interfere with the tests; contraindication or refusal to perform functional brain imaging examinations;

• Absence of caregivers to complete psychological and behavioral scales and/or questionnaires;

• Patient with illiteracy and/or inability to perform psychological and behavioral evaluations;

• Pathologies involving short term vital prognosis (progressive cancer, unstable heart failure, severe liver, kidney or respiratory diseases);

• Primary chronic psychosis or psychotic episodes not associated with the AD pathology;

• Addiction to alcohol or drugs;

• Pregnancy or breast-feeding;

• Epilepsy or other neurodegenerative disorders;

• Vitamin B12 or folic acid deficiency without supplementation;

• Patient participating in another drug trial;

• Thyroid disorders not treated;

• Patient living in institution;

• Patient deprived of liberty by law;

• Patient with contraindications to drugs containing lithium: heart failure, renal failure, Addison disease, and Brugada syndrome.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• NanoLithium® NP03
One administration of 3 mL per day (1.8 mg/day) by depositing 1.5 mL in the gingivo-jugal groove of each cheek with the graduated pipette.
• Placebo
One administration of 3 mL per day (1.8 mg/day) by depositing 1.5 mL in the gingivo-jugal groove of each cheek with the graduated pipette.

Locations

Country	Name	City	State
France	CHU de Lille	Lille
France	CHU de Limoges - Hôpital Dupuytren	Limoges
France	Hôpital De La Timone	Marseille
France	CHU de Montpellier - Hôpital Gui de Chauliac	Montpellier
France	Hôpital Lariboisière	Paris
France	Hôpital Universitaire de Strasbourg	Strasbourg
France	CHU Toulouse - Hôpital La Grave - Cité de la Santé	Toulouse
France	Hôpital des Charpennes - Hospices Civils de Lyon	Villeurbanne

Sponsors (1)

Lead Sponsor	Collaborator
Medesis Pharma SA

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NPI-12 total score	The change from baseline to end of double-blind period (W12) of the NPI-12 total score in the NanoLithium® NP03 arm and in the placebo arm.	12 Weeks
Secondary	Safety of treatment - Adverse effects	The number and types of adverse effects during the study and causal role of the study treatment.	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - associated pathologies	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: associated pathologies: medical conditions start and end date or ongoing, currently treated or not, recorded from patients file.	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - biochemistry - AST/ALT	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: AST/ALT (UI/L)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - biochemistry - Creatinine	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: Creatinine (mg/L or µmol/L)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - biochemistry - Glomerular filtration rate	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: Glomerular filtration rate -Cockcroft or MDRD method - (ml/min/1,73m2)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - biochemistry - B9 vitamin	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: B9 vitamin (µg/L or nmol/L)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - biochemistry - B12 vitamin	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: B12 vitamin (ng/L or pmol/L)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - biochemistry - T3	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: T3 (µg/L or nmol/L)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - biochemistry - T4	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: T4 (µg/L or nmol/L)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - biochemistry - TSH	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: biochemistry: TSH (mlU/L)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - Hematology	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: hematology	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - Lithium blood level	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common biological tests assessment: Clinical laboratory evaluations: lithium blood level	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - Systolic and diastolic blood pressure	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Vital signs: Systolic and diastolic blood pressure (mm Hg)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - Pulse rate	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Vital signs: Pulse rate (beats per minute [bpm])	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - ECG - PR	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Electrocardiogram (ECG): PR interval (msec)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - ECG - QRS	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Electrocardiogram (ECG): QRS interval (msec)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - ECG - QT	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Electrocardiogram (ECG): QT interval (msec)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - ECG - RR	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Electrocardiogram (ECG): RR interval (msec)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - ECG - QTcB	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: Electrocardiogram (ECG): QTcB interval (msec)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - Weight	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: General clinical examination: weight (in Kg)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - Height	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: General clinical examination: height (in cm)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - BMI	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common clinical assessment: General clinical examination: body mass index (BMI) (weight and height will be combined to report BMI in kg/m^2)	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - cognitive signs	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common neurological assessments: Neurological clinical examination: cognitive signs: questions asked to patients/caregiver to detect execution troubles, attention troubles, language, gnosic troubles, praxis, visuo-spacial troubles and temporo-spacial orientation	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - focal neurological signs	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common neurological assessments: Neurological clinical examination: focal neurological signs: questions asked to patients/caregiver to detect extrapyramidal syndrome, pyramidal syndrome, cerebellar syndrome, frontal syndrome, hallucinations, dysautonomia, sensitive system and epilepsy	approximately 1 year
Secondary	Safety of treatment - Clinical assessments - motricity	To assess the safety of NanoLithium® NP03 after 48 weeks of treatment based on common neurological assessments: Neurological clinical examination: motricity: questions asked to patients/caregiver to detect muscular tonus, abnormal movements, reflex, walking troubles, falls, postural troubles, coordination, sphincter and trophic troubles	approximately 1 year
Secondary	Efficacy of treatment_BPSD_NPI-C-IPA	To assess the BPSD at 12 and 48 weeks, change from baseline to week 12 and week 48 on the Neuropsychiatric Inventory - Clinician items mapped to International Psychogeriatric Association (NPI-C-IPA) scale (Units on a Scale).	After 12 and 48 weeks
Secondary	Efficacy of treatment_BPSD_NPI-12	To assess the BPSD at 12 and 48 weeks, score of each item of the Neuropsychiatric Inventory (NPI-12) (Units on a Scale).	After 12 and 48 weeks
Secondary	Efficacy of treatment_cognitive performances - MMSE Score	MMSE score (Units on a Scale).	After 12 and 48 weeks
Secondary	Efficacy of treatment_cognitive performances - CDRS Score	Clinical Dementia Rating Scale (CDRS) score (Units on a Scale).	After 12 and 48 weeks
Secondary	Efficacy of treatment_cognitive performances - ADL Score	Activity of Daily Living (ADL) score (Units on a Scale).	After 12 and 48 weeks
Secondary	Efficacy of treatment_PET-FDG	Cerebral metabolic rate for glucose measured by Positron Emission Tomography-Fluorodeoxyglucose (PET-FDG).	After 12 and 48 weeks
Secondary	Efficacy of treatment_Biomarkers_Peripheral biomarkers	Pathophysiological peripheral biomarkers (amyloid biomarkers, neurofilaments, Tau protein, BDNF) (pg/ml).	After 12 and 48 weeks
Secondary	Efficacy of treatment_Biomarkers_Non-specific biomarkers	Non-specific biomarkers (inflammation cytokines).	After 12 and 48 weeks
Secondary	Efficacy of treatment_Drug compliance	Drug compliance by assessing the number of buccal deposits.	After 12 and 48 weeks